{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:25:15Z","timestamp":1792448715117,"version":"4.5.0"},"reference-count":56,"publisher":"American Society for Clinical Investigation","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,6]]},"abstract":"<jats:p>Systemic lupus erythematosus (SLE) is often associated with exaggerated B cell activation promoting plasma cell generation, immune-complex deposition in the kidney, renal infiltration of myeloid cells, and glomerular nephritis. Type-I IFNs amplify these autoimmune processes and promote severe disease. Bruton\u2019s tyrosine kinase (Btk) inhibitors are considered novel therapies for SLE. We describe the characterization of a highly selective reversible Btk inhibitor, G-744. G-744 is efficacious, and superior to blocking BAFF and Syk, in ameliorating severe lupus nephritis in both spontaneous and IFN\u03b1-accelerated lupus in NZB\/W_F1 mice in therapeutic regimens. Selective Btk inhibition ablated plasmablast generation, reduced autoantibodies, and \u2014 similar to cyclophosphamide \u2014 improved renal pathology in IFN\u03b1-accelerated lupus. Employing global transcriptional profiling of spleen and kidney coupled with cross-species human modular repertoire analyses, we identify similarities in the inflammatory process between mice and humans, and we demonstrate that G-744 reduced gene expression signatures essential for splenic B cell terminal differentiation, particularly the secretory pathway, as well as renal transcriptional profiles coupled with myeloid cell\u2013mediated pathology and glomerular plus tubulointerstitial disease in human glomerulonephritis patients. These findings reveal the mechanism through which a selective Btk inhibitor blocks murine autoimmune kidney disease, highlighting pathway activity that may translate to human SLE.<\/jats:p>","DOI":"10.1172\/jci.insight.90111","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T22:24:53Z","timestamp":1491517493000},"source":"Crossref","is-referenced-by-count":68,"title":["Btk-specific inhibition blocks pathogenic plasma cell signatures and myeloid cell\u2013associated damage in IFN\u03b1-driven lupus nephritis"],"prefix":"10.1172","volume":"2","author":[{"given":"Arna","family":"Katewa","sequence":"first","affiliation":[{"name":"Departments of Immunology Discovery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugang","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Immunology Discovery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason 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